Is PRKD2 p.Ala528Val (c.1583C>T) pathogenic?

PRKD2 p.Ala528Val (c.1583C>T) is classified Uncertain significance in PRKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.1391); Very rare (popmax 0.00322%, nfe).

How common is PRKD2 p.Ala528Val (c.1583C>T) in the general population?

PRKD2 p.Ala528Val (c.1583C>T) is very rare (popmax 0.00322%, nfe) (gnomAD).

What do computational predictors say about PRKD2 p.Ala528Val (c.1583C>T)?

AlphaMissense predicts likely benign (score 0.1391) — an in-silico prediction, not a clinical call.

PRKD2 p.Ala528Val

c.1583C>T · rs772278023 · VCV3218828

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1391 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1391	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP -1.1, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 16 kb · p 2.2e-27 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 38/1,179,888 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00248% 40/1,613,828 alleles · very rare exomes 39/1,461,652 · genomes 1/152,176 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00322%	31,050
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,478

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRKD2
Protein: p.Ala528Val
Coding: c.1583C>T
MANE Select: NM_016457
dbSNP: rs772278023
Type: single nucleotide variant
Location: chr19:46691979 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 528: an α-helix

Full PRKD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PKD2 c.1094+1G>A Pathogenic ★★ same type
PKD2 c.1094+1G>C Pathogenic ★★ same type
PKD2 c.1319+1G>A Pathogenic/Likely pathogenic ★★ same type
PKD2 c.1320-2A>C Pathogenic/Likely pathogenic ★★ same type
PKD2 c.1548+1G>A Pathogenic/Likely pathogenic ★★ same type
PKD2 c.1549-1G>A Pathogenic/Likely pathogenic ★★ same type
PKD2 c.1716+2T>A Pathogenic/Likely pathogenic ★★ same type
PKD2 c.1898+1G>A Pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prkd2-p-ala528val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown